The proposed research is comprised of two parts. The first part is directed toward clarifying the role of phagocytic cells as a tissue site for the metabolism of the thyroid hormones. Here, the influence of induced reticuloendothelial phagocytosis on the kinetics of distribution and metabolism of thyroxine and triiodothyronine will be studied in vivo. Studies will also be conducted with human neutrophils in vitro to elucidate the mechanism of the stimulation by phagocytosis of thyroid hormone deiodination and to define the characteristics of the deiodinative system in this tissue. Additional experiments will be undertaken to evaluate whether thyroid hormone deiodination has a microbicidal action in the human neutrophil. The second part of the proposed research is directed toward clarifying the mechanism of the increased proportion of free thyroxine in the serum of ill patients. Specifically, the question of whether a dialyzable inhibitor of the thyroid hormone-plasma protein interaction is operative in this circumstance will be examined.